AZM475271
Based on 1 Customer Validation
AZM475271 (M475271) is an orally active and selective Src kinase inhibitor. AZM475271 inhibits phosphorylation of c-Src kinase, Lck, c-yes (IC50s = 0.01, 0.03, 0.08 μM, respectively). AZM475271 induces apoptosis. AZM475271 reduces tumor cell proliferation and migration in vitro and in vivo, and reduces microvessel density (MVD). AZM475271 inhibits tumor growth and metastasis. AZM475271 sensitizes tumor cells to the cytotoxic effects of Gemcitabine (HY-17026).
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 99.89%
- No. CAS: 476159-98-5
- Fòrmula: C23H27ClN4O3
- Peso molecular:442.94
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
- Pureza y Documentación
- Referencias
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Help & FAQs
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Apoptosis Compound Library
HY-L003
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Kinase Inhibitor Library
HY-L009
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Protein Tyrosine Kinase Compound Library
HY-L016
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Anti-Cancer Compound Library
HY-L025
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Reprogramming Compound Library
HY-L039
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Orally Active Compound Library
HY-L061
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Anti-Pancreatic Cancer Compound Library
HY-L077
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Angiogenesis-Related Compound Library
HY-L088
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Anti-Prostate Cancer Compound Library
HY-L124
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Anti-Pulmonary Fibrosis Compound Library
HY-L125
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Pain-Related Compound Library
HY-L139
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Membrane Protein-targeted Compound Library
HY-L149
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Highly Selective Inhibitors Library
HY-L158
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Highly Selective Activators Library
HY-L159
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Cell Death Library
HY-L162
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Bioactive Compound Library Max
HY-L181
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MCE Bioactive Compound Library
HY-L001V
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Bioactive Compound Library
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Protein Kinase Compound Library
HY-L196
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Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library
HY-L199
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High-Throughput Bioactive Compound Library
HY-L205
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Posttranslational Modification Library
HY-L226
Actividad biológica
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Lck 0.03 μM (IC50) |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A549 | IC50 |
>25 μM
Compound: AZM475271
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Antiproliferative activity against human A549 cells after 72 hrs by CellTiter 96 aqueous one solution assay
Antiproliferative activity against human A549 cells after 72 hrs by CellTiter 96 aqueous one solution assay
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[PMID: 30562697] |
| A549 | IC50 |
0.48 μM
Compound: 35, M475271
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Inhibition of A549 cell migration by microdroplet migration assay
Inhibition of A549 cell migration by microdroplet migration assay
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[PMID: 17064066] |
| HCT-116 | IC50 |
>25 μM
Compound: AZM475271
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Antiproliferative activity against p53-/- human HCT116 cells after 72 hrs by CellTiter 96 aqueous one solution assay
Antiproliferative activity against p53-/- human HCT116 cells after 72 hrs by CellTiter 96 aqueous one solution assay
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[PMID: 30562697] |
| HCT-116 | IC50 |
>25 μM
Compound: AZM475271
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Antiproliferative activity against p53+/+ human HCT116 cells after 72 hrs by CellTiter 96 aqueous one solution assay
Antiproliferative activity against p53+/+ human HCT116 cells after 72 hrs by CellTiter 96 aqueous one solution assay
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[PMID: 30562697] |
| MCF7 | IC50 |
>25 μM
Compound: AZM475271
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Antiproliferative activity against human MCF7 cells after 72 hrs by CellTiter 96 aqueous one solution assay
Antiproliferative activity against human MCF7 cells after 72 hrs by CellTiter 96 aqueous one solution assay
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[PMID: 30562697] |
| NHDF | IC50 |
>25 μM
Compound: AZM475271
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Antiproliferative activity against human NHDF cells after 72 hrs by CellTiter 96 aqueous one solution assay
Antiproliferative activity against human NHDF cells after 72 hrs by CellTiter 96 aqueous one solution assay
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[PMID: 30562697] |
| NIH3T3 | IC50 |
0.01 μM
Compound: 35, M475271
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Inhibition of human c-Src in NIH3T3 cells
Inhibition of human c-Src in NIH3T3 cells
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[PMID: 17064066] |
| NIH3T3 | IC50 |
0.53 μM
Compound: 35, M475271
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Antiproliferative activity against mouse NIH3T3 cell line transfected with c-SRC
Antiproliferative activity against mouse NIH3T3 cell line transfected with c-SRC
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[PMID: 17064066] |
| Sf9 | IC50 |
5 nM
Compound: 56; AZM475271
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Inhibition of human recombinant Src expressed in baculovirus infected Sf9 insect cells assessed as reduction in phosphorylation of polyglutamic acid/tyrosine incubated for 15 mins by ELISA
Inhibition of human recombinant Src expressed in baculovirus infected Sf9 insect cells assessed as reduction in phosphorylation of polyglutamic acid/tyrosine incubated for 15 mins by ELISA
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[PMID: 30878832] |
AZM475271 inhibits the proliferation of c-Src3T3 (transfected in fibroblast cells, 24 h, IC50 = 0.53 μM) and A549 (72 h, IC50 = 0.48 μM) cells[1][2].
AZM475271 (1-20 μM, 48 h) shows no anti-proliferative effect on L3.6pl human pancreatic carcinoma cells in vitro below 15 μM, but induces cell death at 20 μM[2].
AZM475271 (5 μM, 12 h) induces apoptosis and the effect can be enhanced by combination with Gemcitabine in L3.6pl cells[2].
AZM475271 (0.1-5 μM, 4 h) inhibits L3.6pl cell migration[2].
AZM475271 (1-10 μM, 4 h) demonstrates strong dose-dependent inhibition of Src tyrosine kinase activity in the L3.6pl cell line[2].
AZM475271 effectively blocks TGF-β1-induced chemokinesis of Panc-1 cells and inhibits the high chemokinetic activity of Panc-1 cells with ectopic expression of a constitutively active ALK5T204D mutant. [3].
AZM475271 (10-100 µM, 24-72 h) inhibits SFK in prostate tissues and WPMY-1 cells, reduces α1-adrenergic and neurogenic contraction of prostate strips[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:L3.6pl human pancreatic cancer cells
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Concentration:1, 5, 10, 15, 20 μM
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Incubation Time:48 h
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Result:Showed no anti-proliferative effect on L3.6pl cells in vitro, although a rapid decrease in cell proliferation was detected at high concentrations (> 20 μM).
Microscopic investigation indicated the rapid inhibition of cell proliferation was caused by reduced cell numbers due to therapy-induced cell death.
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Cell Line:L3.6pl human pancreatic cancer cells
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Concentration:5 μM
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Incubation Time:12 h
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Result:Resulting in apoptosis in 12.6%, 11.0%, and 52.2% of the tumor cells in used alone group, Gemcitabine group and combination group, respectively.
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Cell Line:L3.6pl human pancreatic cancer cells
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Concentration:0.1, 1, 5 μM
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Incubation Time:4 h
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Result:Produced significant inhibition of L3.6pl tumor cell migration at 1 and 5μM.
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Cell Line:L3.6pl human pancreatic cancer cells
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Concentration:1, 2.5, 5, 10 μM
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Incubation Time:4 h
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Result:Demonstrated strong dose-dependent inhibition of Src tyrosine kinase activity.
Maximum reduction of Src kinase activity was observed with ≥ 5 μM (4.76-fold reduction).
AZM475271 (50 mg/kg; p.o.; once) has biological effective plasma concentration with 24 hours in healthy nude mice [2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Healthy nude mice[2]
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Dosage:50 mg/kg
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Administration:Oral gavage (p.o.); once
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Result:The plasma concentration was 32.1 μM (14.206 ng/mL), 20 μM (8879 ng/mL), and 11.7 μM (5187 ng/mL) at 2, 6, and 24 hours after p.o..
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Animal Model:Athymic nude mice (injected with 1 X 106 viable L3.6pl cells)[2]
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Dosage:50 mg/kg
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Administration:Oral gavage (p.o.); once daily for 32 days
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Result:The median tumor volume was significantly less than that in control mice.
After combination therapy, primary pancreatic tumor volume was significantly less than that seen with Gemcitabine alone.
The incidence of liver metastasis was markedly reduced.
Did not significantly change animal weight when used alone, but reduced animal weight combined with Gemcitabine.
Has antiproliferative effect alone and in combination with Gemcitabine.
Induce apoptosis in pancreatic carcinoma cells in vivo, maximum apoptotic effect was observed in the combination with Gemcitabine.
Reduced microvessel density (MVD) alone and no significant difference in combination with Gemcitabine.
Chemical Information
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No. CAS 476159-98-5
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Appearance Solid
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Peso molecular 442.94
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Fòrmula C23H27ClN4O3
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Color White to off-white
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SMILES
CN1CCC(COC2=CC3=NC=NC(NC4=CC(OC)=CC=C4Cl)=C3C=C2OC)CC1
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Synonyms
M475271
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Solvente y solubilidad
DMSO : ≥ 42 mg/mL (94.82 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Pureza y Documentación
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Ficha de datos (285 KB)
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SDS (479 KB)
- English - EN (479 KB)
- Français - FR (479 KB)
- Deutsch - DE (479 KB)
- Norwegian - NO (479 KB)
- Español - ES (479 KB)
- Swedish - SV (479 KB)
- Italian - IT (479 KB)
- Korean - KR (479 KB)
- Portuguese - PT (479 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Plé PA, et al. Discovery of a new class of anilinoquinazoline inhibitors with high affinity and specificity for the tyrosine kinase domain of c-Src. J Med Chem. 2004 Feb 12;47(4):871-87. [Content Brief]
[2]. Yezhelyev MV, et al. Inhibition of SRC tyrosine kinase as treatment for human pancreatic cancer growing orthotopically in nude mice. Clin Cancer Res. 2004 Dec 1;10(23):8028-36. [Content Brief]
[3]. Bartscht T, et al. TGF-β Signal Transduction in Pancreatic Carcinoma Cells is Sensitive to Inhibition by the Src Tyrosine Kinase Inhibitor AZM475271. Anticancer Agents Med Chem. 2017;17(7):966-972. [Content Brief]
[4]. Wang Y, et al. Smooth muscle contraction and growth of stromal cells in the human prostate are both inhibited by the Src family kinase inhibitors, AZM475271 and PP2. Br J Pharmacol. 2016 Dec;173(23):3342-3358. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.2576 mL | 11.2882 mL | 22.5764 mL | 56.4411 mL |
| 5 mM | 0.4515 mL | 2.2576 mL | 4.5153 mL | 11.2882 mL | |
| 10 mM | 0.2258 mL | 1.1288 mL | 2.2576 mL | 5.6441 mL | |
| 15 mM | 0.1505 mL | 0.7525 mL | 1.5051 mL | 3.7627 mL | |
| 20 mM | 0.1129 mL | 0.5644 mL | 1.1288 mL | 2.8221 mL | |
| 25 mM | 0.0903 mL | 0.4515 mL | 0.9031 mL | 2.2576 mL | |
| 30 mM | 0.0753 mL | 0.3763 mL | 0.7525 mL | 1.8814 mL | |
| 40 mM | 0.0564 mL | 0.2822 mL | 0.5644 mL | 1.4110 mL | |
| 50 mM | 0.0452 mL | 0.2258 mL | 0.4515 mL | 1.1288 mL | |
| 60 mM | 0.0376 mL | 0.1881 mL | 0.3763 mL | 0.9407 mL | |
| 80 mM | 0.0282 mL | 0.1411 mL | 0.2822 mL | 0.7055 mL |
AZM475271 Related Classifications
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